The role of nerve-muscle interactions on muscle and motoneurone development

The importance of early postnatal nerve-muscle interaction for normal development is examined in this thesis. It has been found that temporary disconnection of muscles and motoneurones by nerve crush during early postnatal life permanently alters the properties of muscles and motoneurones. The morphological and physiological changes that occur during early stages of reinnervation of neonatal fast and slow muscles are discussed in the first part of the thesis. Although the motor nerve reaches the fast extensor digitorum longus (EDL) muscle at the same time as the slow soleus muscle, the soleus muscle shows a more rapid recovery. The permanent effects on the fast muscles anterior (TA) and extensor digitorum longus (EDL) of interrupting interaction with their nerves during early postnatal life by nerve crush 3 or 9 mm away from them are discussed. The results show that the shorter the period of interruption of nerve-muscle interaction during early postnatal life, the better is the recovery of reinnervated muscles. The effects of neonatal sciatic crush on the efferent inputs to surviving motoneurones after reinnervation has been studied. Stimulation of efferent nerves ipsilaterally or contralaterally produces a greater reflex response in the reinnervated than in the control muscle, indicating that the activation of motoneurones is changed by neonatal nerve injury. In the final part of the thesis the possibility of the involvement of calcium in the death of 50% of motoneurones of the sciatic pool after sciatic nerve crush at birth has been studied. The results show that a calcium chelating agent at the site of the nerve injury marginally improves motoneurone survival. The possibility that this may be due to local effects on regenerating axons is discussed

Using Functional Near Infrared Spectroscopy (fNIRS) to study dynamic stereoscopic depth perception

The parietal cortex has been widely implicated in the processing of depth perception by many neuroimaging studies, yet functional near infrared spectroscopy (fNIRS) has been an under-utilised tool to examine the relationship of oxy- ([HbO]) and de-oxyhaemoglobin ([HbR]) in perception. Here we examine the haemodynamic response (HDR) to the processing of induced depth stimulation using dynamic random-dot-stereograms (RDS). We used fNIRS to measure the HDR associated with depth perception in healthy young adults (n = 13, mean age 24). Using a blocked design, absolute values of [HbO] and [HbR] were recorded across parieto-occipital and occipital cortices, in response to dynamic RDS. Control and test images were identical except for the horizontal shift in pixels in the RDS that resulted in binocular disparity and induced the percept of a 3D sine wave that 'popped out' of the test stimulus. The control stimulus had zero disparity and induced a 'flat' percept. All participants had stereoacuity within normal clinical limits and successfully perceived the depth in the dynamic RDS. Results showed a significant effect of this complex visual stimulation in the right parieto-occipital cortex (p < 0.01, η(2) = 0.54). The test stimulus elicited a significant increase in [HbO] during depth perception compared to the control image (p < 0.001, 99.99 % CI [0.008-0.294]). The similarity between the two stimuli may have resulted in the HDR of the occipital cortex showing no significant increase or decrease of cerebral oxygenation levels during depth stimulation. Cerebral oxygenation measures of [HbO] confirmed the strong association of the right parieto-occipital cortex with processing depth perception. Our study demonstrates the validity of fNIRS to investigate [HbO] and [HbR] during high-level visual processing of complex stimuli

Measuring visual cortical oxygenation in diabetes using functional near-infrared spectroscopy

Aims: Diabetes mellitus affects about 6% of the world’s population, and the chronic complications of the disease may result in macro- and micro-vascular changes. The purpose of the current study was to shed light on visual cortical oxygenation in diabetic individuals. We then aimed to compare the haemodynamic response (HDR) to visual stimulation with glycaemic control, given the likelihood of diabetic individuals suffering from such macro- and micro-vascular insult. Methodology: Thirty participants took part in this explorative study, fifteen of whom had diabetes and fifteen of whom were non-diabetic controls. The HDR, measured as concentrations of oxyhaemoglobin [HbO] and deoxyhaemoglobin [HbR], to visual stimulation was recorded over the primary visual cortex (V1) using a dual-channel oximeter. The stimulus comprised a pattern-reversal checkerboard presented in a block design. Participants’ mean glycated haemoglobin (HbA1c) level (±SD) was 7.2±0.6% in the diabetic group and 5.5±0.4% in the non-diabetic group. Raw haemodynamic data were normalised to baseline, and the last 15 s of data from each ‘stimulus on’ and ‘stimulus off’ condition were averaged over seven duty cycles for each participant. Results: There were statistically significant differences in ∆[HbO] and ∆[HbR] to visual stimulation between diabetic and non-diabetic groups (p&lt;0.05). In the diabetic group, individuals with type 1 diabetes displayed an increased [HbO] (p&lt;0.01) and decreased [HbR] (p&lt;0.05) compared to their type 2 counterparts. There was also a linear relationship between both ∆[HbO] and ∆[HbR] as a function of HbA1c level (p&lt;0.0005). Conclusions: Our findings suggest that fNIRS can be used as a quantitative measure of cortical oxygenation in diabetes. Diabetic individuals have a larger HDR to visual stimulation compared to non-diabetic individuals. This increase in ∆[HbO] and decrease in ∆[HbR] appears to be correlated with HbA1c level

Effects of glaucoma and snoring on cerebral oxygenation in the visual cortex: a study using functional Near Infrared Spectroscopy (fNIRS)

Purpose: The purpose of this study was to investigate the effects of snoring and glaucoma on the visual Haemodynamic Response (HDR) using functional Near Infrared Spectroscopy (fNIRS). Methods: We recruited 8 glaucoma patients (aged 56-79), 6 habitual snorers (aged 26-61) and 10 healthy control participants (aged 21-78). Glaucoma patients were of varying subtypes and under care of ophthalmologists. Prior to testing visual acuity, blood pressure, heart rate and a medical history were taken. HDRs were recorded over the primary visual cortex (V1) using a reversing checkerboard paradigm. Results &amp; Discussion: All participants showed the characteristic increase of Oxyhaemoglobin concentration ([HbO]) and decrease of Deoxyhaemoglobin concentration ([HbR]) during visual stimulation (p &lt; 0.001, η2 = 0.78). Despite this, there were signifi cant group differences with a large effect size (η2 = 0.28). During visual stimulation normal participants had greater [HbO] compared to snorers and glaucoma patients (p &lt; 0.01). Both glaucoma patients and snorers presented with comparable HDR for [HbO] and [HbR] in V1. Importantly, during visual stimulation, the increased [HbO] in glaucoma patients correlated well with their visual fi elds and self-reported activities of daily living (r = -0.98, r = -0.82, p &lt; 0.05). Both glaucoma patients and snorers presented with an attenuated HDR in V1. Our results suggest a possible vascular link between these conditions

Editorial: From Pedagogic Research to Embedded E-Learning

This Special Issue of Reflecting Education arises from the work of the PREEL project (From Pedagogic Research to Embedded e-Learning) at the Institute of Education from 2006-2008. This project was one of nine HEA/JISC (Higher Education Academy and Joint Information Systems Committee) Pilot Pathfinder Projects and followed on from our involvement in the Pilot Benchmarking of e-Learning Programme. In the benchmarking exercise we identified a lack of coordination between research and practice in e-learning at the IoE as one of our crucial weaknesses, and so our Pilot Pathfinder project concentrated on this theme of building links between e-learning research and practice

Measuring the foveal avascular zone in diabetes: a study using optical coherence tomography angiography

AIMS/INTRODUCTION: Diabetes is a global issue that currently affects 425 million people worldwide. One observable microvascular complication of this condition is a change in the foveal avascular zone (FAZ). In this study, we used optical coherence tomography angiography to investigate the effect of diabetes on the FAZ. MATERIALS AND METHODS: A total of 11 participants with diabetes and 11 participants without diabetes took part in this study. Participants in both groups were matched for age (P = 0.217) and sex (P = 0.338), and had no history of ocular disease. Macular optical coherence tomography angiography (OCT‐A) scans of participants’ right and left eyes were taken. Glycosylated hemoglobin (HbA(1c)) and blood glucose levels were also measured. The FAZ area was manually segmented at the levels of the superficial capillary plexus (FAZ(SCP)) and deep capillary plexus (FAZ(DCP)). RESULTS: There was a strong relationship between the FAZ area of participants’ right and left eyes (P ≤ 0.001) in both diabetes and non‐diabetes groups. In the diabetes group, the FAZ(SCP) (P = 0.047) and FAZ(DCP) (P = 0.011) areas was significantly larger than in the non‐diabetes group. Moreover, multiple linear regression analysis predicted a 0.07‐mm(2) increase in the FAZ(SCP) and FAZ(DCP) areas of individuals with diabetes for every 1% increase in their HbA(1c) level. CONCLUSIONS: Our findings show that there is enlargement of the FAZ in individuals with diabetes compared with individuals without diabetes. In the diabetes group, this enlargement appears to be correlated with HbA(1c) level. OCT‐A imaging could, therefore, be a useful tool to monitor the FAZ and identify potential early microvasculopathy in diabetes

Environmental and behavioural interventions for reducing physical activity limitation and preventing falls in older people with visual impairment

BACKGROUND: Impairment of vision is associated with a decrease in activities of daily living. Avoidance of physical activity in older adults with visual impairment can lead to functional decline and is an important risk factor for falls. The rate of falls and fractures is higher in older people with visual impairment than in age‐matched visually normal older people. Possible interventions to reduce activity restriction and prevent falls include environmental and behavioral interventions. OBJECTIVES: We aimed to assess the effectiveness and safety of environmental and behavioral interventions in reducing physical activity limitation, preventing falls and improving quality of life amongst visually impaired older people. SEARCH METHODS: We searched CENTRAL (including the Cochrane Eyes and Vision Trials Register) (Issue 2, 2020), Ovid MEDLINE, Embase and eight other databases to 4 February 2020, with no language restrictions. SELECTION CRITERIA: Eligible studies were randomized controlled trials (RCTs) and quasi‐randomized controlled trials (Q‐RCTs) that compared environmental interventions, behavioral interventions or both, versus control (usual care or no intervention); or that compared different types of environmental or behavioral interventions. Eligible study populations were older people (aged 60 and over) with irreversible visual impairment, living in their own homes or in residential settings. To be eligible for inclusion, studies must have included a measure of physical activity or falls, the two primary outcomes of interest. Secondary outcomes included fear of falling, and quality of life. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (686 participants) conducted in five countries (Australia, Hungary, New Zealand, UK, US) with follow‐up periods ranging from two to 12 months. Participants in these trials included older adults (mean age 80 years) and were mostly female (69%), with visual impairments of varying severity and underlying causes. Participants mostly lived in their homes and were physically independent. We classified all trials as having high risk of bias for masking of participants, and three trials as having high or unclear risk of bias for all other domains. The included trials evaluated various intervention strategies (e.g. an exercise program versus home safety modifications). Heterogeneity of study characteristics, including interventions and outcomes, (e.g. different fall measures), precluded any meta‐analysis. Two trials compared the home safety modification by occupational therapists versus social/home visits. One trial (28 participants) reported physical activity at six months and showed no evidence of a difference in mean estimates between groups (step counts: mean difference (MD) = 321, 95% confidence interval (CI) ‐1981 to 2623; average walking time (minutes): MD 1.70, 95% CI ‐24.03 to 27.43; telephone questionnaire for self‐reported physical activity: MD ‐3.68 scores, 95% CI ‐20.6 to 13.24; low‐certainty of evidence for each outcome). Two trials reported the proportion of participants who fell at six months (risk ratio (RR) 0.76, 95% CI 0.38 to 1.51; 28 participants) and 12 months (RR 0.59, 95% CI 0.43 to 0.80, 196 participants) with low‐certainty of evidence for each outcome. One trial (28 participants) reported fear of falling at six months, using the Short Falls Efficacy Scale‐International, and found no evidence of a difference in mean estimates between groups (MD 2.55 scores, 95% CI ‐0.51 to 5.61; low‐certainty of evidence). This trial also reported quality of life at six months using 12‐Item Short Form Health Survey, and showed no evidence of a difference in mean estimates between groups (MD ‐3.14 scores, 95% CI ‐10.86 to 4.58; low‐certainty of evidence). Five trials compared a behavioral intervention (exercise) versus usual activity or social/home visits. One trial (59 participants) assessed self‐reported physical activity at six months and showed no evidence of a difference between groups (MD 9.10 scores, 95% CI ‐13.85 to 32.5; low‐certainty of evidence). Three trials investigated different fall measures at six or 12 months, and found no evidence of a difference in effect estimates (RRs for proportion of fallers ranged from 0.54 (95% CI 0.29 to 1.01; 41 participants); to 0.93 (95% CI 0.61 to 1.39; 120 participants); low‐certainty of evidence for each outcome). Three trials assessed the fear of falling using Short Falls Efficacy Scale‐International or the Illinois Fear of Falling Measure from two to 12 months, and found no evidence of a difference in mean estimates between groups (the estimates ranged from ‐0.88 score (95% CI ‐2.72 to 0.96, 114 participants) to 1.00 score (95% CI ‐0.13 to 2.13; 59 participants); low‐certainty of evidence). One trial (59 participants) assessed the European Quality of Life scale at six months (MD ‐0.15 score, 95% CI ‐0.29 to ‐0.01), and found no evidence of a clinical difference between groups (low‐certainty of evidence). AUTHORS' CONCLUSIONS: There is no evidence of effect for most of the environmental or behavioral interventions studied for reducing physical activity limitation and preventing falls in visually impaired older people. The certainty of evidence is generally low due to poor methodological quality and heterogeneous outcome measurements. Researchers should form a consensus to adopt standard ways of measuring physical activity and falls reliably in older people with visual impairments. Fall prevention trials should plan to use objectively measured or self‐reported physical activity as outcome measures of reduced activity limitation. Future research should evaluate the acceptability and applicability of interventions, and use validated questionnaires to assess the adherence to rehabilitative strategies and performance during activities of daily living

Reduced haemodynamic response in the ageing visual cortex measured by absolute fNIRS

The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds